Of all the various methods aiming to inhibit abnormal collagen accumulation (fibrosis), the only clinically-promising approach is the interference with collagen crosslinking. This proposal deals exclusively with: 1) lysyl oxidases involved in the synthesis of allysin, 2) with drugs inhibiting the activity of this enzyme (osteolathyrogens) and 3) other situations characterized by crosslinking of collagen and elastin. New methods of isolation, purification and assaying lysyl oxidases from various tissues are proposed with the aim to characterize the enzymes in enzymological terms and to analyze factors regulating it. New aspects in the effect of osteolathyrogens, mainly of B-Aminopropionitrile (BAPN), are proposed indicating that lower dose of BAPN inhibits lysyl oxidase to the same extent as high dose of BAPN, which in addition acts non-specifically (toxic effect) on tissue metabolism, thus increasing pool of soluble collagen even more by enhancing collagen degradation. Another aspect relates to BAPN-metal cations interaction and the role of monamino oxidases and their inhibitors in the control of efficacy of lathyrogens. Activity and extractability of lysyl oxidases, physical state of collagen under various physiological (ontogeny) and pathological situations (wound healing, lung silicosis, arteriosclerosis, retrolental fibroplasia, cleft palate) will be studied. In similar models of fibrosis or abnormal collagen behavior we will study the effect of systemically administered BAPN and locally administered BAPN-polymer compound as far as dose, duration and reversibility of the effect on lysyl oxidase and collagen crosslinking is concerned. The aim of this proposal is to form a scientific basis for clinical use of some lathyrogens. A multidisciplinary approach is suggested involving biochemical, organic synthesis, biological, pathological and morphological methods of analysis. BIBLIOGRAPHIC REFERENCES: Misiorowski, R. L., Ulreich, J. B. and Chvapil, M.: A microassay for lysyl oxidase activity. Analytical Biochem. 71: 186-192. 1976. Fleisher, J. H., Arem, A. J., Chvapil, M. and Peacock, E. E.: Metabolic disposition of B-aminopropionitrile in the rat. Proc. Soc. Exp. Biol. Med. 152: 469-474, 1976.